Our long-term goal is to understand the factors that govern the ability or inability of axons to respond to altered sensory input by reorganizing their connections. The visual system of Xenopus frogs is an appropriate system for studying such effects for several reasons: 1) Binocular connections to the optic tectum undergo major reorganization during development, and successful establishment of matching connections from the two eyes depends upon visual input during a critical period of early life. 2) Connections can be systematically reorganized in response to abnormal visual input, such as from rotation of one eye. 3) The ability to reorganize connections normally is lost in adults. This difference provides a tool for identifying the permissive characteristics present in young but not older animals 4) This plasticity can be restored in adults by application of low doses of N-methyl-D-aspartate. In order to understand the mechanisms underlying plasticity, we need a more complete pharmacological description of the tectum. The glutamatergic character of the axons that bring input directly from the contralateral retina has been established by several labs, with particular attention to the N-methyl-D-aspartate receptor and its role in control of intradendritic calcium. However, the cholinergic axons that bring input indirectly from the ipsilateral eye have been much less well studied. Since their activity is important for the activity-mediated establishment of ipsilateral maps, we need to know which tectal cells are their targets, what sorts of acetylcholine receptors are present on those cells, and whether cholinergic activation of those cells results in increases in intracellular calcium. Electrophysiological and imaging studies will reveal the nature of the acetylcholine receptors and their influence on intracellular calcium. These data will also help to clarify the possible role of acetylcholine receptors that are found on retinotectal terminals and that may modulate transmitter release by those synapses. This research will contribute to our understanding of the mechanisms by which reorganization of the brain occurs during early life and after alterations of sensory input or various types of trauma in later life. In particular, the growing evidence of the importance of glutamate receptors will be enhanced by a better characterization of the role of acetylcholine in control of stabilization of synapses.